The lung has been shown to perform important nonrespiratory functions, among which are the removal and metabolism of circulating biogenic amines and drugs. Since impairment of this capacity by environmental agents could contribute to their toxicity, the effects of selected environmental toxicants on pulmonary clearance is being examined. Pretreatment of rats with the pneumotoxicant, paraquat, decreases the ability of lung to remove perfused 5-hydroxytryptamine. Chronic, intermittent exposure of rats to carbon monoxide (250 ppm, 8 hr/day, 5 days/week for 6 weeks) did not alter the ability of their isolated lungs to remove or metabolize perfused 5-hydroxytryptamine. Studies of metabolism in broken cell preparations have led many to believe that drug clearance by lung in vivo is minor compared to that of liver. Therefore, clearance of 5-hydroxytryptamine was compared in intact liver and lung at physiological perfusion rates in order to assess the relative contribution of these organs to clearance in vivo. These studies indicate that although rat lung contains only 8% as much monoamine oxidase as rat liver, clearance of 5HT by isolated lungs perfused at flows occurring in vivo was three times that of perfused livers. These results suggest that despite its relative deficiency in degradative enzyme the rat lung plays a major role in the total body clearance of circulating 5-hydroxytryptamine. Similarly, studies in which mescaline clearance by rabbit lung and liver was predicted from enzyme kinetic data suggests that lung may be important in the clearance in vivo of this xenobiotic agent.